昭和大学薬学雑誌 第 2 巻 第 1 号 2011 年 調査報告㩷 新たに同定されたカリウムチャネルの立体構造解析と留学記㩷 㩷 ᣣਅㇱศ↵㩷 ᤘᄢቇ⮎ቇㇱ⮎ຠ‛ℂൻቇᢎቶ㩷 㩷 ⷐ ᣦ㩷 㧷㧗࠴ࡖࡀ࡞ಽሶߪ㧘ࠞ࠙ࡓࠗࠝࡦ㧔㧷㧗㧕ߛߌࠍ㜞ㅦ߆ߟㆬᛯ⊛ߦㅢߔಽሶߢ㧘⚦⢩৻⥸ߩ 㕒ᱛ⤑㔚ߩᓮ߿㧘⥝ᅗᕈ⚦⢩ߩ⊒Ἣࡄ࠲ࡦߩቯߦ㊀ⷐߥᓎഀࠍᨐߚߔ㧚㩷 ౝะ߈ᢛᵹᕈ㧷㧗࠴ࡖࡀ࡞㨇㪠㫅㫎㪸㫉㪻㫃㫐㩷㫉㪼㪺㫋㫀㪽㫐㫀㫅㪾㩷㫇㫆㫋㪸㫊㫊㫀㫌㫄㩷㪺㪿㪸㫅㫅㪼㫃㫊㩷 㧔㪢㫀㫉㧕㨉ߪ㧘⒳⚦ߩޘ⢩ᄖ㧷㧗 Ớᐲਅߦ߅ߡ㧘ਥߣߒߡ㧷㧗ߩᐔⴧ㔚એਅߢ㐿߈㧘ౝะ߈㔚ᵹࠍㅢߔ࡙࠾ࠢߥ㧷㧗࠴ࡖࡀ࡞ ߢࠆ㧚㪢㫀㫉 ߪ㧘᭽ߥޘᲥ⚛ߩ࠲ࠥ࠶࠻ߢࠅ㧘ߎߩ࠴ࡖࡀ࡞ߩਇ⺞ߪ᭽∔ߥޘᖚߦߟߥ߇ࠆߎ ߣ߇⍮ࠄࠇߡࠆࠃ߁ߦ㧘↢ౝߢ↢ℂቇ⊛ߦ㊀ⷐߥᄙߊߩᓎഀࠍṶߓߡࠆߚ㧘ᄙߊߩ⎇ⓥ ⠪߆ࠄᵈ⋡ࠍ㓸ߡࠆ㧚ᧄ⎇ⓥߩ⋡⊛ߪ㧘߹ߢߦࠄ߆ߦߥߞߡࠆ㧷㧗࠴ࡖࡀ࡞ߩਛߢ㧘 ᦨㄭᣂߚߦࠢࡠ࠾ࡦࠣߐࠇߚᣂⷙ㧷㧗࠴ࡖࡀ࡞ߩ㜞ಽ⸃⢻ߢߩ┙᭴ㅧ⸃ᨆࠍ⋡ᜰߔ㧚⋡⊛ߣ ߒߡࠆ࠲ࡦࡄࠢ⾰ߪ㧷㧗․⇣⊛ㅘㆊᯏ᭴߇ઁߩ㧷㧗࠴ࡖࡀ࡞ߣ⇣ߥࠆߣ⠨߃ࠄࠇߡࠆ㧚㩷 ⋡⊛࠲ࡦࡄࠢ⾰ߪ㧘⤑࠲ࡦࡄࠢ⾰ߢࠆߩߢ㧘⤑ߣ⋧↪ࠍߔࠆߚߩਇṁᕈ㗔ၞࠍࠎߢ ࠆߚ 㫀㫅㩷 㫍㫀㫋㫉㫆 ߢߩᛒ߇㔍ߒ㧚ߘߎߢ⤑࠲ࡦࡄࠢ⾰ߩ⎇ⓥ߇ㅴࠎߢࠆ 㪦㫏㪽㫆㫉㪻 ᄢቇߦ⇐ቇ ߒ㧘ขࠅᛒࠍቇࠎߛ㧚᭽ߥޘนṁൻ᧦ઙࠍ⹜ߔߎߣߢ㧘⋡⊛࠲ࡦࡄࠢ⾰ߩนṁൻߦᚑഞߒ㧘ߐ ࠄߦ㪊⒳㘃ߩࠢࡠࡑ࠻ࠣࡈࠖࠍⴕ߁ߎߣߢ㧘♖ߦᚑഞߒߚ㧚♖ߒߚ࠲ࡦࡄࠢ⾰ߦኻߒߡ⚿ ᥏ൻࠬࠢ࠾ࡦࠣࠍⴕߞߚߣߎࠈ㧘ᓸዊ⚿᥏ࠍᓧࠆߎߣߦᚑഞߒߚ㧚㩷 㩷 㪢㪼㫐㩷㪮㫆㫉㪻㫊㧦㪦㫏㪽㫆㫉㪻 ᄢቇ㧘᭴ㅧ⸃ᨆ㧘ࠞ࠙ࡓ࠴ࡖࡀ࡞㩷 㩷 ࠆ ߎ ߣ ߆ ࠄޟᄢቇߩਛߦ↸߇ࠆࠇࠊ⸒ߣޠ ✜ ⸒ ߡࠆ㧚㪦㫏㪽㫆㫉㪻 ᄢቇߢߪޟቇㇱޠࠫ࠶ࠞޟߣޠ ⪺⠪߇㪉㪇㪇㪐ᐕ㪍߆ࠄ㪉㪇㪈㪇ᐕ㪈㪉߹ߢቴຬᢎ ߩੑ㊀᭴ㅧߦߥߞߡ߅ࠅ㧘ߘߩోࠍᄢቇ߇⛔ ߣߒߡ⇐ቇߒߚ 㪦㫏㪽㫆㫉㪻 ᄢቇߪ㧘ࡠࡦ࠼ࡦߩർ㧘 ߒߡࠆ㧚ߪޠࠫ࠶ࠞޟᣣᧄߢߪߥߓߺߩߥ 㔚ゞߢ㪈ᤨ㑆ඨ߶ߤߩ〒㔌ߦࠅ㧘ᣇߦ✭߿߆ ߽ߩߢ㧘ࠗࠡࠬߩᄢቇߢ߽ߩޠࠫ࠶ࠞޟᐲ ߦᐢ߇ࠆࠦ࠶࠷ࡥ࡞࠭ߩਐ㒺߆ࠄᵹࠇߚ᳓ࠍ ࠍᱷߒߡࠆߩߪ 㪦㫏㪽㫆㫉㪻 ᄢቇߣ 㪚㪸㫄㪹㫉㫀㪻㪾㪼 ᄢቇߩ ࠹ࡓ࠭Ꮉ߇㓸߈ߞߚߚࠅߦ⟎ߔࠆ 㪦㫏㪽㫆㫉㪻 ߺߢࠆ㧚◲නߦ⺑ߔࠆߣ㧘ޟቇㇱ࠺ࠞࠕ߇ޠ Ꮢౝߦࠆ㧚ฎߊ߆ࠄቇ↢ߩⴝߣߒߡฬߢ㧘ᤋ ࡒ࠶ࠢߥ㕙㧘ࠇߘ߇ޠࠫ࠶ࠞޟએᄖߩ↢ᵴో⥸ ↹ࡂࡐ࠶࠲ߩ⥰บ㧘ᓇ႐ᚲߣ߁ߎߣ߆ ߢࠆ㧚㪦㫏㪽㫆㫉㪻 ᄢቇߩߪޠࠫ࠶ࠞޟ㪋㪇એࠅ㧘 ࠄࠊ߆ࠆࠃ߁ߦ㧘ⴝਗߺߪᧄᒰߦ⟤ߒߊ㧘 ฦ ࠞ ቇ↢ߩኾ⑼⋡ࠍ㒢ቯߒߡࠆࠞ࠶ࠫ߿ᄢቇ ࠶ ࠫ ߪ ߘ ߩ ਛ ᔃ ㇱ ߦ ὐ ߒ 㧘ᄢ ቇ ߩ ᱧ 㒮↢ߩߺߩࠞ࠶ࠫߥߤ․ᓽ߽᭽ߢޘ㧘㗿ᤨߩ ผࠍ‛⺆ࠆᑪ‛߇ߚࠆᚲߦ߰ࠇߡ ┹₸߿⚻༡⁁ᘒ߽᭽ࠆߢޘ㧔࿑㪈㧕㧚ฦࠞ࠶㩷 ― 101 ― 昭和大学薬学雑誌 第 2 巻 第 1 号 2011 年 㪦㫏㪽㫆㫉㪻 ᄢቇߪ㧘࠴ࡘ࠻ࠕ࡞ߣ߫ࠇࠆੱᜰ ዉᕈߢߒߞ߆ࠅߣߒߚᢎ⢒ࠪࠬ࠹ࡓࠍᜬߞߡ ࠆ㧚৻ੱߩᜰዉᢎቭ߇৻ੱ߹ߚߪੑੱߩቇ↢ࠍฃ ߌᜬߜ㧘㪉ੱ㪊⣉ߢතᬺࠍ⋡ᜰߔ㧚㩷 ⪺⠪ߩᚲዻ⎇ⓥቶߪ㧘ᆎ 㪧㪿㫐㫊㫀㫆㫃㫆㪾㫐 ߦዻߒߡ ߚ߇㧘ඨᐕᓟ㧘㪧㪿㫐㫊㫀㪺㫊 ߦᒁߒࠍߒߚ㧚⒖േవ ߩ 㪧㪿㫐㫊㫀㪺㫊 ߪߣߡ߽ᄢ߈ߥ 㪛㪼㫇㪸㫉㫋㫄㪼㫅㫋 ߢࠅ㧘⎇ ⓥࠍㅴࠆߚߩࠨࡐ࠻߇లታߒߡࠆ㧔࿑㪉㧕㧚 㩷 㩷 ࿑㧝 㪦㫏㪽㫆㫉㪻 ᄢቇߩࠞ࠶ࠫߩ৻ߟ㧘㪢㪼㪹㫃㪼㩷㪚㫆㫃㫃㪼㪾㪼 ߩ౮⌀ 㩷 ࠫߦߪ࠳ࠗ࠾ࡦࠣࡎ࡞߿␞ၴ㧘㘩ၴ㧘⺣ቶ ߥߤࠍ߃ߟߌࠄࠇߡࠆ㧚ฦࠞ࠶ࠫߦߪ⒳ޘ ߩࠢࡉᵴേ߇ࠅ㧘ࠞ࠶ࠫኻ᛫ߩᄢળߥߤࠍ ⴕߞߡࠆ㧚ฬߥࠞ࠶ࠫߩ৻ߟߦ㧘ਇᕁ⼏ߩ ࿖ߩࠕࠬߩ⠪㧘࡞ࠗࠬࠠࡖࡠ࡞ߩりࠞ ࠶ࠫߢ㧘‛⺆ߩ⥰บߢࠅ㧘߹ߚᤋ↹ࡂࡐ࠶ ࠲ߩᓇߦᄙߊࠊࠇߡࠆࠢࠗࠬ࠻࠴ ࿑㧞 㪧㪿㫐㫊㫀㪺㫊㩷㩿㪚㫃㪸㫉㪼㫅㪻㫆㫅㩷㪣㪸㪹㫆㫉㪸㫋㫆㫉㫐㪀㩷 ߩᩞ⥢㩷 ࡖ࠴߇ࠆ㧚ࠢࠗࠬ࠻̒࠴ࡖ࠴ౝߪ৻⥸ߩ ੱ߽߅㊄ࠍᛄ߁ߎߣߢቇߔࠆߎߣ߇ߢ߈ࠆߩ 㪧㪿㫐㫊㫀㫆㫃㫆㪾㫐㧘㪧㪿㫐㫊㫀㪺㫊 ߦ 㪦㫏㪽㫆㫉㪻 ᄢቇߩർ᧲ㇱߦ ߢ㧘ቇ↢ߩߺߛߌߢߥߊⷰశቴ߽ᄙߊ㧘ߣߡ߽ߦ ࠆࠨࠗࠛࡦࠬࠛࠕౝߦࠆ㧚ࠨࠗࠛࡦࠬࠛ ߉ࠊߞߡࠆ㧚㩷 ࠕ ߦ ߪ 㧘 ో 㪈㪇㪌 ਛ 㧘 ඨ ಽ ㄭ ߊ ߩ 㪋㪌 ߩ 㪦㫏㪽㫆㫉㪻 ᄢቇߩޟቇㇱߪߦޠ㧘㪋ߟߩ 㪻㫀㫍㫀㫊㫀㫆㫅 ߇ࠅ㧘 㪻㪼㫇㪸㫉㫋㫄㪼㫅㫋㫊㧘㩷㫊㫌㪹㪄㪻㪼㫇㪸㫉㫋㫄㪼㫅㫋㫊 ߇ኒ㓸ߒߡࠆᄢ ߘߩਛߦ㧘㪈㪇㪇એߩ 㪻㪼㫇㪸㫉㫋㫄㪼㫅㫋㫊㪃㩷 㫊㫌㪹㪄㪻㪼㫇㪸㫉㫋㫄㪼㫅㫋㫊㪃㩷 ቇߩਛᔃࠛࠕߢࠆ㧚ߘߩਛᔃࠛࠕߩᄢ߈ 㪽㪸㪺㫌㫃㫋㫀㪼㫊㪃㩷㫊㫌㪹㪄㪽㪸㪺㫌㫃㫋㫀㪼㫊㪃㩷㫀㫅㫊㫋㫀㫋㫌㫋㪼㫊㪃㩷㪺㪼㫅㫋㫉㪼㫊 ߇ࠆ㧚߶߷ ㇱಽࠍභࠆ 㪧㪿㫐㫊㫀㪺㫊 ߪ㧘⇇ᦨవ┵ߩ⎇ⓥࠍⴕ ోߡߩᩞ⥢ߦߪࠞࡈࠚ߇ઃߡ߅ࠅ㧘ᣂ⡞߿㔀 ߞߡ߅ࠅ㧘⎇ⓥᢎ⢒ߩਔ㕙ߢ࠻࠶ࡊࠢࠬࠍ ࠍ⺒ࠎߛࠅ㧘㔀⺣ࠍᭉߒࠎߛࠅ㧘ᢎቭ߇ቇ↢ߦീ ࠆᄢቇߩ㗻ߣ߫ࠇࠆ 㪻㪼㫇㪸㫉㫋㫄㪼㫅㫋 ߩ৻ߟߢࠆ㧚 ᒝࠍᢎ߃ߚࠅ㧘⋧⺣ߦਸ਼ࠆߥߤ㧘ࠦࡒࡘ࠾ࠤࠪ ᛛⴚ⠪ࠍ 㪻㪼㫇㪸㫉㫋㫄㪼㫅㫋 ߆ࠄ㈩ዻߐࠇߡࠆߎߣ߿㧘 ࡚ࡦ߇ขࠅ߿ߔⅣႺ߇ᢛߞߡࠆ㧚㪚㪸㫄㪹㫉㫀㪻㪾㪼 ᢥᚱౕ߿ታ㛎ᶖ⠻ຠߥߤࠍ 㪻㪼㫇㪸㫉㫋㫄㪼㫅㫋 ߆ࠄᔅⷐߥ ᄢቇߣߪᒝࠗࡃ࡞㑐ଥߦࠅ㧘ਔᩞߩ㑆ߢߪ㧘 ߣ߈ߦߔߋߦήᢱߢᡰ⛎ߐࠇࠆߥߤ⎇ⓥࠍⴕ߁ ࠬࡐ࠷ߥߤฦ⒳ߩⷫༀ⹜ว߇㗫❥ߦⴕࠊࠇࠆ㧚 ߚߩⅣႺ߇ᢛߞߡࠆ㧚㪧㪿㫐㫊㫀㪺㫊 ߩਛߢߪ㧘Ფᣣ ਛߢ߽ߣࠅࠊߌฬߥߩߪ㧘Ფᐕᤐߦࡠࡦ࠼ࡦߩ ߣ߁߶ߤࡒ࠽߇ࠅ㧘ฦ⥝ޘߩࠆࡒ ࠹ࡓ࠭Ꮉߢⴕࠊࠇࠆࡏ࠻ࠬ㧔ࠟ࠶࠲㧕ߢ ࠽ߦෳടߔࠆ㧚ࡒ࠽ߩᓟߪᔅߕࡄ࠹ࠖ ࠆ㧚ࠬࡐ࠷ߛߌߢߪߥߊ㧘㪦㫏㪽㫆㫉㪻 ᄢቇౝߢ ߇ࠅ㧘ࡢࠗࡦ㧘ࠦࡅ㧘⚃⨥㧘ࠬ࠽࠶ࠢ⩻ሶ㧘 㪚㪸㫄㪹㫉㫀㪻㪾㪼 ᄢቇߩ⎇ⓥ⠪߿ᢎ⢒⠪ߩ⻠Ṷ߇ⴕࠊࠇ ࠨࡦ࠼ࠗ࠶࠴㧘ࠤࠠ╬߇ᝄ⥰ࠊࠇࠆ㧚ࡒ࠽ ࠆߥߤ㧚⎇ⓥቇߦ㑐ߒߡ߽ᵹ߇⋓ࠎߢࠆ㧚㩷 ᓟߩࡄ࠹߽ࠖᏨ⠪߇ᄙߊ㧘ᄙߊߩ⎇ⓥ⠪߆ ᄢቇߩቇᦼߪ㪈㪇߆ࠄ㪈㪉㧘㪈߆ࠄ㪊㧘㪋 ࠄᗧ߿ࠕ࠼ࡃࠗࠬࠍࠁߞߊࠅߣ⡞ߊߎߣ߇ߢ ߆ࠄ㪍ߩฦቇᦼ㪏ㅳ㑆ߩ㪊ቇᦼߩߺߢࠆ㧚ߎߩ ߈ࠆ㧚㩷 ⍴ቇᦼߦᚑᨐࠍߍࠆߚߦ㧘ߚߊߐࠎࠆ࿑ ߹ߚ㧘㪻㪼㫇㪸㫉㫋㫄㪼㫅㫋 ࠍ߃ߡ㧘ᄢቇౝߢߩห⎇ ᦠ㙚ߪߤߎ߽ߟ߽ḩຬߢ⑳⺆ߪ৻ߟ߽ߥ㧚 ⓥ߇㕖Ᏹߦᵴ⊒ߢࠅ㧘⪺⠪߇ᚲዻߒߚ⎇ⓥቶ߇ ― 102 ― 昭和大学薬学雑誌 第 2 巻 第 1 号 2011 年 ࠹ࡑߦߒߡࠆ㧷㧗࠴ࡖࡀ࡞ߩ⎇ⓥࠍⴕ߁ߦᒰ 㔍ߒߊ㧘㫀㫅㩷㫍㫀㫍㫆 ߩ⎇ⓥߪㅴࠎߢ߈ߚ߇㧘᭴ㅧ⸃ᨆ ߚࠅ㧘ᄢቇౝߩ㪌ߟߩ⎇ⓥቶߣห⎇ⓥࠍⴕߞߡ ࠍ 㫀㫅㩷 㫍㫀㫋㫉㫆 ߩ⎇ⓥߪ㧘߹ࠅㅴࠎߢߥ߆ߞ ࠆ㧚ᐕߦ৻ᐲ㧘ห⎇ⓥࠍⴕߞߡࠆ⎇ⓥ⠪߇ ߚ㧚ߒ߆ߒ㧘ㄭᐕ⇇㕙ᵴᕈߩ㐿⊒߇ㅴߺ㧘⤑࠲ ోຬ㓸߹ࠅ㧘ࡒ࠽߇㐿߆ࠇࠆ㧚ߘߎߢ㧘⎇ⓥ ࡦࡄࠢ⾰ߩ᭴ㅧ⸃ᨆߩ⺰ᢥ߇⪺ฬߥ㔀ߩ⚕㕙 ߩㅴߺౕว㧘⚿ᨐߥߤࠍႎ๔ߒ㧘ᗧߩ឵߿ ࠍߦ߉ࠊߔߥߤ㧘߿ࡎ࠶࠻ߥ⎇ⓥಽ㊁ߣߥߞߚ㧚 㩷 ⧎ߩ൬ࠍ༦ߢߘࠇ߇ࡃߢࠆߣಽ߆ߞ ᓟߩ⸘↹ࠍࠆ㧚㩷 ᢎ⢒㕙ߦ㑐ߒߡ߽ᜰዉ߇ᔀᐩߒߡ߅ࠅ㧘ᢎຬߛ ߚࠅ㧘ᾲ߽ߩߦ⸅ࠇߚߣ߈ߦ⊛ߦᚻࠍᒁߞ ߌߢߥߊ㧘ࡐࠬ࠼ࠢߥߤߩ⎇ⓥ⠪߽㧘㪧㪿㫐㫊㫀㪺㫊 ㄟࠆᤨߦ㧘㥦߿ᚻߩ⚻ߪ⣖ߦାภࠍㅍࠆߚ ߦዻߒߡࠆᄙߊߩࡔࡦࡃ߇ቇ↢ࠍᜰዉߔࠆ ߩࠗࠝࡦࠍߒ㧘ὼࠆߴ߈ᔕ߇⣖߆ࠄㅍࠅ 㓙ߩᵈᗧὐ߿ࠦ࠷ߥߤߩ⻠⟵ࠍฃߌࠆߛߌߢߥ ߐࠇߡࠆ㧚⚻⚦⢩ߪାภࠍㅍࠆḰߣߒߡ㧘 ߊޔታ㓙ߦᜰዉࠍⴕ㧘ᡷༀὐࠍᜰ៰ߐࠇࠆߥߤ ࠞ࠙ࡓࠗࠝࡦ㧔㧷㧗㧕ࠍౝㇱߦ⫾߃㧘࠽࠻࠙ ߩታᛛࠍࡢ࡚ࠢࠪ࠶ࡊߦෳടߔࠆ㧚㩷 ࡓࠗࠝࡦ㧔㪥㪸㧗㧕ࠍㆬᛯ⊛ߦឃߒߡࠆ㧚ߎࠇ 㩷 ߦࠃߞߡ⚦⢩⤑ౝᄖߢ㧘㪥㪸㧗ߣ㧷㧗ߦ㑐ߒߡᄢ߈ߥ Ớᐲ൨㈩߇᧪㧘⤑㔚ࠍ↢ߓߐߖߡࠆ㧚⥝ᅗ ᤨߦߪାภࠍㅍࠆߚߦ㧘⚻⚦⢩ߩ㕙ߦࠆ 㪥㪸㧗࠴ࡖࡀ࡞߇㐿ߊߎߣߢ㧘⚦⢩ౝߦ 㪥㪸㧗߇ᵹ ߒ㧘⤑ౝᄖߩ㔚Ꮕߪᷫዋߔࠆ㧔⣕ಽᭂ㧕㧚ᰴߦ 㧷㧗࠴ࡖࡀ࡞߇㐿ߡ㧷㧗߇ឃߐࠇ㧘㔚߇రߦ ᚯࠆ㧚ߎࠇࠄߩ࠴ࡖࡀ࡞ߪ⤑ౝᄖߩ㔚Ꮕߦᔕ ߒ㧘㔚߇ᄌൻߔࠆߎߣߢ㐿ߊ㧚ߘߩߚ㧘⚻ ⚦⢩ߩᧃ┵ߢ࠴ࡖࡀ࡞߇㐿߈ࠗࠝࡦ߇ᵹߔࠆ ߣߔߋߦ㧘⤑ߩ㔌ࠇߚ႐ᚲߦࠆ࠴ࡖࡀ࡞߽㐿 ߆ࠇࠆ㧚ߘߩ⚿ᨐ㧘࠴ࡖࡀ࡞ࠍ㐿ߊᔕ߇⚻⚦ ࿑㪊 㪪㫋㪼㫇㪿㪼㫅㩷㪫㫌㪺㫂㪼㫉 ⎇ⓥቶߩࡔࡦࡃ㩷 ⪺⠪߇⇐ቇߒߚ⎇ⓥቶߪ㧘㪏ฬߩ⎇ⓥ⠪߇ዻߒ ߡࠆ㧔࿑㪊㧕㧚 ޟ㧷㧗࠴ࡖࡀ࡞⎇ࠍޠⓥኻ⽎ߣߒߡ ⢩ࠍࠅᛮߌ㧘⚻ାภ߇ᧃ┵߳ߣવࠊࠆߎߣߦ ߥࠆ㪈㪀㪃㩷㪉㪀㧚㩷 ࠆߎߣߩߺㅢߒߡࠆ߇㧘ኾ㐷ಽ㊁ߪ⊝㧘⇣ ࠴ࡖࡀ࡞ಽሶߩ৻⒳ߢࠆ㧷㧗࠴ࡖࡀ࡞ಽሶߪ㧘 ߥߞߡࠆ㧚એਅߦ⪺⠪߇⇐ቇਛߦᓧߚ⚿ᨐࠍ◲ 㧷㧗ߛߌࠍ㜞ㅦ߆ߟㆬᛯ⊛ߦㅢߔಽሶߢ㧘ࡃࠢ࠹ නߦ⺑ߔࠆ㧚㩷 ࠕ߆ࠄࡅ࠻ߦ⥋ࠆ߹ߢ᭽⚦ߩࡊࠗ࠲ߥޘ⢩ౝߢ⊒ ⤑࠲ࡦࡄࠢ⾰ߪ㧘ࡅ࠻ࠥࡁࡓߩ⚂㪊㪇㧑ࠍභߡ ߒ㪊㪀㪃㪋㪀㧘⚦⢩৻⥸ߩ㕒ᱛ⤑㔚ߩᓮ߿㧘⥝ᅗᕈ⚦⢩ ߅ࠅ㧘⚦⢩⤑ࠍᮮಾࠆ‛⾰ߩャㅍ㧘⚦⢩㑆ធ⌕㧘 ߩ⊒Ἣࡄ࠲ࡦߩቯߦ㊀ⷐߥᓎഀࠍᨐߚߔ㪌㪀㪃㩷 㪍㪀㧚㧷㧗 㕙⼂㧘⚦⢩㛽ᩰធ⌕㧘ࠪࠣ࠽࡞વ㆐㧘㉂⚛ᵴ ࠴ࡖࡀ࡞ߩᄌ⇣ߪ㧘⣖ߢߪߡࠎ߆ࠎ㧘৻ᤨ⊛ߥㆇേ ᕈߥߤߦ㊀ⷐߥᓎഀࠍߪߚߒߡࠆ㧚↢‛㧔⚦⢩㧕 ᄬ⺞∝㧘⡊ߢߪ㔍⡬㧘ᔃ⤳ߢߪਇᢛ⣂㧘╭⡺ߢߪ╭ ߪ㧘ᄖㇱߣᖱႎ‛⾰ࠛࡀ࡞ࠡߩ߿ࠅߣࠅࠍ ᵄേ∝߿╭ήജ∝㧘⣢⤳ߢߪ㜞ⴊ㧘⤟⤳ߢߪࠗࡦ ⚦⢩⤑ࠍߒߡ߅ߎߥߞߡࠆߎߣ߆ࠄ㧘⤑࠲ࡦ ࠬࡦㆊಽᴲ∝ߥߤࠍᒁ߈ߎߔߎߣ߇⍮ࠄࠇߡ ࡄࠢ⾰ߩᄢㇱಽ߇ߦ‛↢ޟᔅ㗇ࠆߢޠน⢻ᕈ߇ ࠆ㧚㧷㧗࠴ࡖࡀ࡞ߦߪ㪉⒳㘃ࠅ㧘৻ߟߪ⣕ಽᭂᓟ㧘 ࠆ㧚㧘ක⮎ຠߩ࠲ࠥ࠶࠻ߩ⚂㪌㪇㧑߇⤑࠲ 㔚ࠍరߦᚯߔߚߦ⚦⢩ౝߦ㧷㧗ࠗࠝࡦࠍᵹߐ ࡦࡄࠢ⾰ߢࠆߣࠊࠇ㧘ᓟᵈ⋡ߐࠇ㧘߹ߔ߹ ߖౝะ߈㔚ᵹࠍᵹߔ㪉࿁⤑⽾ㅢဳߩౝะ߈ᢛᵹᕈ㧷 ߔ⎇ⓥ߇⋓ࠎߦߥࠆ࠲ࡦࡄࠢ⾰⟲ߩ߭ߣߟߢ 㧗 ࠆ㧚ߒ߆ߒ㧘⤑࠲ࡦࡄࠢ⾰ߪ↢⤑ߣ⋧↪ࠍ ߔࠆߚߦ㧘⚦⢩ᄖߦ㧷㧗ࠗࠝࡦࠍឃߔࠆ㧘㪍࿁⤑ ߔࠆߚߩਇṁᕈ㗔ၞࠍᜬߞߡࠆߚᛒ߇ ⽾ㅢဳߩ⤑㔚ଐሽ㧷㧗࠴ࡖࡀ࡞㧔࿑㪌㧕㩷 ࠴ࡖࡀ࡞㪎㪀㩷㪃㪏㪀㧔࿑㪋㧕ߣౝะ߈㔚ᵹߩⴕ߈ㆊ߉ࠍୃᱜ ― 103 ― 昭和大学薬学雑誌 第 2 巻 第 1 号 2011 年 ߇ࠆ㧚ߎߩੑߟߩ㧷㧗࠴ࡖࡀ࡞߇⚦⢩ౝߩᓸᅱߥ P䊦䊷䊒 㧷㧗Ớᐲࠍ⺞▵ߒߡࠆ㧚㩷 ⚦⢩ᄖ ౝ ะ ߈ ᢛ ᵹ ᕈ 㧷 㧗 ࠴ ࡖ ࡀ ࡞ 㪲㪠㫅㫎㪸㫉㪻㫃㫐㩷 㫉㪼㪺㫋㫀㪽㫐㫀㫅㪾㩷 S5 㫇㫆㫋㪸㫊㫊㫀㫌㫄㩷㪺㪿㪸㫅㫅㪼㫃㫊㩷㩿㪢㫀㫉㧕㨉ߪ㧘ਥߣߒߡ㧷㧗ߩᐔⴧ㔚 S6 એਅߢ㐿߈㪐㧕㧘ౝะ߈㔚ᵹࠍㅢߔ࡙࠾ࠢߥ㧷㧗࠴ ࡖࡀ࡞ߢࠆ㪈㪇㧕㧚ౝะ߈ᢛᵹᕈ㧷㧗࠴ࡖࡀ࡞ߪ㧘᭽ޘ ⚦⢩ౝ ߥᲥ⚛ߩ࠲ࠥ࠶࠻ߢࠅ㧘ߎߩ࠴ࡖࡀ࡞ߩਇ⺞ߪ ᭽∔ߥޘᖚߦߟߥ߇ࠆߎߣ߇⍮ࠄࠇߡࠆࠃ߁ߦ㧘 ↢ౝߢ↢ℂቇ⊛ߦ㊀ⷐߥᄙߊߩᓎഀࠍṶߓߡࠆ ࿑㪋 ౝะ߈㔚ᵹࠍᵹߔ㪉࿁⤑⽾ㅢဳߩౝะ߈ᢛᵹᕈ㧷㧗࠴ ࡖࡀ࡞ߩ㪉ᰴ᭴ㅧ㩷 㧗 ౝะ߈ᢛᵹᕈ㧷 ࠴ࡖࡀ࡞ߪ㪉ߟߩ⚦⢩⤑⽾ㅢ㗔ၞߣ㪈ߟ ߩࠗࠝࡦㆬᛯᕈࡈࠖ࡞࠲ࠍᜬߞߡࠆ㧚ߎߩࠨࡉ࡙࠾࠶ ࠻߇ࡎࡕࠆߪࡋ࠹ࡠ㪋㊂ࠍᒻᚑߒ㧘ᯏ⢻⊛ߥ 㪢㫀㫉 ࠴ࡖ ࡀ࡞ࠍ᭴ᚑߒߡࠆ㧚㩷 㧷㧗࠴ࡖࡀ࡞ߩ㊀ⷐᕈࠍ␜ߔ৻ߣߒߡ㧘ౝะ߈ᢛ ᵹᕈ㧷㧗࠴ࡖࡀ࡞ߣ㘃ૃߩ᭴ㅧࠍᜬߟࡃࠢ࠹ࠕ↱ ᧪㧷㧗࠴ࡖࡀ࡞㧔㪢㪺㫊㪘㧕ߩ┙᭴ㅧࠍࠄ߆ߦߒߚ 㪤㪸㪺㪢㫀㫅㫅㫆㫅 ඳ჻ߦኻߔࠆ㪉㪇㪇㪊ᐕᐲࡁࡌ࡞ൻቇ⾨ߩ P䊦䊷䊒 ⚦⢩ᄖ ߚ㧘ᄙߊߩ⎇ⓥ⠪߆ࠄᵈ⋡ࠍᶎ߮ߡࠆ㧔࿑㪍㧕㧚 ਈ߇ߍࠄࠇࠆ㪈㪈㪀㪃㩷 㪈㪉㪀㧚ߘࠇએ㒠㧘ᄙߊߩ⎇ⓥ⠪߇ ᭽ߥޘ⒳㘃ߩ 㪢㫀㫉 ߩ┙᭴ㅧࠍࠄ߆ߦߒߡ߈ߚ 㧔࿑ 㪎㧕㪈㪉㪀㪄㪉㪈㪀㧚㩷 + + S5 S1 S2 S3 S4 + S6 + Zhou Y., et.al. 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Nature, 471 336-340 (2011) ࿑㪎 ߹ߢߦࠄ߆ߦߥߞߡࠆ㧘ઍ⊛ߥ 㪢㫀㫉 ߩ┙ ᭴ㅧ 㨇 㧔ᢥ₂㪈㪉㨪㪈㪐㧕ࠃࠅᡷᄌ㨉㩷 ⋡ ⊛ 㽲㽳㽴 KB6.1 G Y G KB7.1 G Y G KB8.1 G Y G KcsA G Y G 㧗 㧷㧗㧔r 㪔㪈㪅㪊㪊Έ㧕ߪ 㪥㪸㧗㧔r 㪔㪇㪅㪐㪌Έ㧕ࠃࠅ߽ᄢ ߈㧚ߒ߆ߒ㧷㧗࠴ࡖࡀ࡞ߢߪ㧘㧷㧗ߪ 㪥㪸㧗ࠃࠅ߽ ታߦ㪈㪇㪋ㅘㆊᕈ߇㜞㧚ߟ߹ࠅ㧘㧷㧗࠴ࡖࡀ࡞ߪ ᄢ߈ߥ㧷㧗ߛߌࠍ㕖Ᏹߦㆬᛯ⊛ߦㅘㆊߐߖࠆ㧚ᧄ ࿑㪍 ౝะ߈ᢛᵹᕈ㧷 ࠴ࡖࡀ࡞㧔㪢㫀㫉㪙㪸㪺㪈㪅㪈㧕ߩ┙᭴ㅧߣ ࡈࠖ࡞࠲㗔ၞߩᄢ࿑㩷 Ꮐ࿑ߪࠄ߆ߦߥߞߡࠆౝะ߈ᢛᵹᕈ㧷㧗࠴ࡖࡀ ࡞ߩ৻ߟ㧘㪢㫀㫉㪙㪸㪺㪈㧚㪈ߩ┙᭴ㅧ㧚ฝ࿑ߩᄢߒߡࠆ 㗔ၞߪ㧷㧗ࠗࠝࡦㆬᛯᕈߦ㑐ࠊߞߡࠆ 㪪㪼㫃㪼㪺㫋㫀㫍㫀㫋㫐㩷 㪩㪼㪾㫀㫆㫅㪅 ฝਅ࿑ߪ㧘㧷㧗ㆬᛯߦ㑐ࠊߞߡࠆࠕࡒࡁ㉄ᱷၮߢ㧘ᄙߊ ߩ㧷㧗࠴ࡖࡀ࡞ߢሽߐࠇߡࠆ߇㧘⪺⠪߇࠲ࠥ࠶࠻ߣ ߒߡࠆ࠲ࡦࡄࠢ⾰ߪ㧘㧷㧗ㆬᛯㇱ߇⇣ߥߞߡࠆߚ㧘 ᣂߒㆬᛯᯏ᭴߇⠨߃ࠄࠇࠆ㧚㩷 ⎇ⓥߢߪ㧘߹ߢߦࠄ߆ߦߥߞߡࠆ㧷㧗࠴ ࡖࡀ࡞ߩਛߢ㧘ᦨㄭᣂߚߦࠢࡠ࠾ࡦࠣߐࠇߚᣂ ⷙ㧷㧗࠴ࡖࡀ࡞ߩ㜞ಽ⸃⢻ߢߩ┙᭴ㅧ⸃ᨆࠍ⋡ ᜰߔ㧚⋡⊛ߣߒߡࠆ࠲ࡦࡄࠢ⾰ߪ㧷㧗․⇣⊛ㅘ ㆊᯏ᭴߇ઁߩ㧷㧗࠴ࡖࡀ࡞ߣ⇣ߥࠆߣ⠨߃ࠄࠇߡ ࠆ㧚㩷 ― 104 ― 昭和大学薬学雑誌 第 2 巻 第 1 号 2011 年 ⤑࠲ࡦࡄࠢ⾰ߪ㧘↢ౝߢ㊀ⷐߥ߈ࠍᜂߞߡ ⻢ߚߒ߹ߔ㧚㩷 ࠆߚ㧘ഃ⮎ߩ⎇ⓥࠍⴕ߁ߦߚࠅ㧘㕖Ᏹߦ㊀ ห⎇ⓥߩᔟ⻌ߣৼካߥߏᜰዉࠍ⾦ࠅ߹ߒߚ㧘 ⷐߥ࿃ሶߢࠆߚ㧘⪺⠪ߪ㧘⤑࠲ࡦࡄࠢ⾰ߩ⚿ ⚿᥏ൻታ㛎㨄✢࿁᛬ታ㛎ߦ㓙ߒߡߏදജ㗂ߚ ᥏᭴ㅧ⸃ᨆߦᒝߊ⥝ࠍᜬߞߡߚ㧚ߒ߆ߒ㧘↢ 㪦㫏㪽㫆㫉㪻 ᄢቇ 㪙㫀㫆㪺㪿㪼㫄㫀㫊㫋㫉㫐 ߩ 㪜㪻㫎㪸㫉㪻㩷㪣㫆㫎㪼 ඳ჻㧘น ⤑ߣ⋧↪ࠍߔࠆߚߩਇṁᕈ㗔ၞࠍᜬߞ ṁൻታ㛎ߦ㓙ߒߡߏᜰዉࠍ⾦ࠅ߹ߒߚ 㪦㫏㪽㫆㫉㪻 ᄢ ߡࠆߚᛒ߇㔍ߒߊ㧘᭴ㅧ⸃ᨆࠍ 㫀㫅㩷㫍㫀㫋㫉㫆 ቇ 㪙㫀㫆㪺㪿㪼㫄㫀㫊㫋㫉㫐㩷 ߩ 㪪㫀㫄㫆㫅㩷㪥㪼㫎㫊㫋㪼㪸㪻 ඳ჻ߦᷓߊᗵ⻢ ߩ⎇ⓥߪ㧘߹ࠅㅴࠎߢߥ߆ߞߚ㧚ߘߎߢ㧘⤑ ߚߒ߹ߔ㧚㩷 ࠲ࡦࡄࠢ⾰ߩ⎇ⓥ߇ㅴࠎߢࠆ 㪦㫏㪽㫆㫉㪻 ᄢቇౝߩ 㧷㧗࠴ࡖࡀ࡞ߩኾ㐷ኅߢࠆ 㪪㫋㪼㫇㪿㪼㫅㩷 㪡㩷 㪫㫌㪺㫂㪼㫉 ߩ ᢥ ₂ ⎇ⓥቶߦ⇐ቇߒ㧘⤑࠲ࡦࡄࠢ⾰ࠍ 㫀㫅㩷 㫍㫀㫋㫉㫆 ߢᛒ߁ 㪈㪀㩷 㪙㫀㪺㪿㪼㫋㪃㩷 㪛㪅㪃㩷 㪟㪸㪸㫊㫊㪃㩷 㪝㪅㩷 㪘㪅㪃㩷 㪡㪸㫅㪃㩷 㪣㪅㩷 㪰㪅㪑㩷 㪤㪼㫉㪾㫀㫅㪾㩷 ࡁ࠙ࡂ࠙ࠍቇࠎߛ㧚㩷 㪽㫌㫅㪺㫋㫀㫆㫅㪸㫃㩷 㫊㫋㫌㪻㫀㪼㫊㩷 㫎㫀㫋㪿㩷 㫊㫋㫉㫌㪺㫋㫌㫉㪼㫊㩷 㫀㫅㫎㪸㫉㪻㪄㫉㪼㪺㫋㫀㪽㫀㪼㫉㩷 㪢㪂㩷 㪺㪿㪸㫅㫅㪼㫃㫊㪅㩷 㩷 Nat. ᣇ ᴺ 㫆㪽㩷 Rev. 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Chem. 㪉㪏㪌㪃㩷㪋㪇㪎㪌㪋㪄㪍㪈㩷㩿㪉㪇㪈㪇㪀㩷 ࠍᓧࠆߎߣߦᚑഞߒ㧘ࠗࠡࠬߩశᣉ⸳ߢ㨄 㪊㧕㩷 㪟㫆㪃㩷 㪢㪅㪃㩷 㪥㫀㪺㪿㫆㫃㫊㪃㩷 㪚㪅㩷 㪞㪅㪃㩷 㪣㪼㪻㪼㫉㪼㫉㪃㩷 㪮㪅㩷 㪡 et al.㪑㩷 ✢࿁᛬ታ㛎ࠍⴕߞߚᚲ㧘࠲ࡦࡄࠢ⾰ߩ⚿᥏ߢࠆ 㪚㫃㫆㫅㫀㫅㪾㩷㪸㫅㪻㩷㪼㫏㫇㫉㪼㫊㫊㫀㫆㫅㩷㫆㪽㩷㪸㫅㩷㫀㫅㫎㪸㫉㪻㫃㫐㩷㫉㪼㪺㫋㫀㪽㫐㫀㫅㪾㩷 ߎߣ߇⏕ߢ߈ߚ㧚㩷 㪘㪫㪧㪄㫉㪼㪾㫌㫃㪸㫋㪼㪻㩷㫇㫆㫋㪸㫊㫊㫀㫌㫄㩷㪺㪿㪸㫅㫅㪼㫃㪅㩷Nature,㩷㪊㪍㪉㪃㩷 㪊㪈㪄㪊㪏㩷㩿㪈㪐㪐㪊㪀㩷 ⚿ᨐ߅ࠃ߮⠨ኤ 㪋㧕㩷 㪢㫌㪹㫆㪃㩷 㪰㪅㪃㩷 㪙㪸㫃㪻㫎㫀㫅㪃㩷 㪫㪅㪡㪅㪃㩷 㪡㪸㫅㪃㩷 㪰㪅㪥㪅㪃㩷 et al.㪑㩷 ᓧࠄࠇߡࠆ⚿᥏ൻ᧦ઙߢߪ㧘᭴ㅧ⸃ᨆ 㪧㫉㫀㫄㪸㫉㫐㩷㫊㫋㫉㫌㪺㫋㫌㫉㪼㩷㪸㫅㪻㩷㪽㫌㫅㪺㫋㫀㫆㫅㪸㫃㩷㪼㫏㫇㫉㪼㫊㫊㫀㫆㫅㩷㫆㪽㩷㪸㩷 ࠍⴕ߁ߚߩ࠺࠲߇ዋߥߩߢ㧔ಽ⸃⢻߇ૐ 㫄㫆㫌㫊㪼㩷 㫀㫅㫎㪸㫉㪻㩷 㫉㪼㪺㫋㫀㪽㫀㪼㫉㩷 㫇㫆㫋㪸㫊㫊㫀㫌㫄㩷 㪺㪿㪸㫅㫅㪼㫃㪅㩷 㧕㧘ߎࠇ߆ࠄߪ⚿᥏߇ᓧࠄࠇߡࠆ⚿᥏ൻ᧦ઙ Nature㪃㩷㪊㪍㪉㪃㩷㪈㪉㪎㪄㪈㪊㪊㩷㩿㪈㪐㪐㪊㪀㩷 ߩᴉᲚߩỚᐲࠍᄌ߃ࠆ㧘㪘㪻㪻㫀㫋㫀㫍㪼㩷 㪪㪺㫉㪼㪼㫅 ࠍⴕ߁ 㪌㧕㩷 㪛㪸㫊㪺㪸㫃㪃㩷 㪥㪅㪃㩷 㪪㪺㪿㫉㪼㪹㫄㪸㫐㪼㫉㪃㩷 㪮㪅㩷 et al.㪑㩷 㪘㫋㫉㫀㪸㫃㩷 㪞㩷 ߥߤᦨㆡߥ⚿᥏ൻ᧦ઙࠍត⚝ߒ㧘㜞ಽ⸃⢻ߩ࠺ 㫇㫉㫆㫋㪼㫀㫅㪄㪸㪺㫋㫀㫍㪸㫋㪼㪻㩷㪢㪂㩷㪺㪿㪸㫅㫅㪼㫃㪑㩷㪼㫏㫇㫉㪼㫊㫊㫀㫆㫅㩷㪺㫃㫆㫅㫀㫅㪾㩷 ࠲ࠍᓧࠆߎߣࠍ⋡ᜰߔ㧚㩷 㪸㫅㪻㩷㫄㫆㫃㪼㪺㫌㫃㪸㫉㩷㫇㫉㫆㫇㪼㫉㫋㫀㪼㫊㪅㩷Proc. Natl. Acad. Sci. USA, 㪐㪇㪃㩷㪈㪇㪉㪊㪌㪄㪈㪇㪉㪊㪐㩷㩿㪈㪐㪐㪊㪀㩷 ⻢ ㄉ 㪍㧕㩷 㪤㪸㫋㫊㫌㪻㪸㪃㩷 㪟㪅㪑㩷 㪦㫇㪼㫅㪄㫊㫋㪸㫋㪼㩷 㫊㫌㪹㫊㫋㫉㫌㪺㫋㫌㫉㪼㩷 㫆㪽㩷 㫀㫅㫎㪸㫉㪻㫃㫐㩷 㫉㪼㪺㫋㫀㪽㫐㫀㫅㪾㩷 㫇㫆㫋㪸㫊㫊㫀㫌㫄㩷 㪺㪿㪸㫅㫅㪼㫃㫊㩷 㫉㪼㫍㪼㪸㫃㪼㪻㩷 ᧄ⎇ⓥߪ㧘⪺⠪߇ 㪦㫏㪽㫆㫉㪻 ᄢቇ 㪧㪿㫐㫊㫀㪺㫊 ߩ 㪪㫋㪼㫇㪿㪼㫅㩷 㪫㫌㪺㫂㪼㫉㩷 ⎇ⓥቶߦ߅ߡⴕߞߚ⒳ߩޘታ㛎߮᭴ 㪹㫐㩷㫄㪸㪾㫅㪼㫊㫀㫌㫄㩷㪹㫃㫆㪺㫂㩷㫀㫅㩷㪾㫌㫀㫅㪼㪸㪄㫇㫀㪾㩷㪿㪼㪸㫉㫋㩷㪺㪼㫃㫃㫊㪅㩷J. ㅧ⸃ᨆߦၮߠߡᚑߒߚ߽ߩߢࠅ㧘ߘߩ㑆ᄙ Physiol.,㩷㪊㪐㪎㪃㩷㪉㪊㪎㪄㪉㪌㪏㩷㩿㪈㪐㪏㪏㪀㩷 ߊߩᣇߩޘ᷷߆ߏᡰេߦࠃߞߡᡰ߃ࠄࠇߡ߈ 㪎㧕㩷 㪢㫌㫉㪸㫋㪸㪃㩷㪟㪅㩷㪫㪅㪃㩷㪚㪿㪼㫅㪾㪃㩷㪮㪅㩷㪮㪅㪃㩷㪘㫉㫉㪸㪹㫀㫋㪃㩷㪚㪅㪧㪅㪃㩷et ߹ߒߚ㧚ߎߎߦᗵ⻢ߩᗧࠍߒߚߣᕁ߹ߔ㧚㩷 al㪅㪑㩷㪫㪿㪼㩷㫉㫆㫃㪼㩷 㫆㪽㩷㫋㪿㪼㩷㪺㫐㫋㫆㫇㫃㪸㫊㫄㫀㪺㩷㫇㫆㫉㪼㩷㫀㫅㩷㫀㫅㫎㪸㫉㪻㩷 ߏᄙᔔߦ߽߆߆ࠊࠄߕᤤᄛࠍࠊߕᤨ㑆ࠍഀ߈ᧄ 㫉㪼㪺㫋㫀㪽㫀㪺㪸㫋㫀㫆㫅㩷㫆㪽㩷㪢㫀㫉㪉㪅㪈㩷㪺㪿㪸㫅㫅㪼㫃㫊㪅㩷J. Gen. Physiol. ⎇ⓥ߳ߩߏᡰេߏᜰዉࠍ⾦ࠅ㧘ᧄ⎇ⓥࠍᚑഞ߳ߣዉ 㪈㪊㪇㪃㩷㪈㪋㪌㪄㪈㪌㪌㩷㩿㪉㪇㪇㪎㪀㩷 ߡߊߛߐ߹ߒߚ 㪪㫋㪼㫇㪿㪼㫅㩷 㪡㩷 㪫㫌㪺㫂㪼㫉 ⻠Ꮷߦෘߊᓮ 㪏㧕㩷 㪧㪼㪾㪸㫅㪃㩷 㪪㪅㪃㩷 㪘㫉㫉㪸㪹㫀㫋㪃㩷 㪚㪅㪃㩷 㪱㪿㫆㫌㪃㩷 㪮㪅㪃㩷 et al.:㩷 ␞↳ߒߍ߹ߔ㧚߹ߚ㧘ᄙᄢߥߏᜰዉ㧘ߏഥ⸒ࠍ⾦ 㪚㫐㫋㫆㫇㫃㪸㫊㫄㫀㪺㩷 㪻㫆㫄㪸㫀㫅㩷 㫊㫋㫉㫌㪺㫋㫌㫉㪼㫊㩷 㫆㪽㩷 㪢㫀㫉㪉㪅㪈㩷 㪸㫅㪻㩷 ࠅ߹ߒߚ⎇ⓥຬߩ⊝᭽㧘㪭㪸㫊㫊㫀㫃㫀㫐㩷㪙㪸㫍㫉㫆 ඳ჻ߦᷓߊᗵ 㪢㫀㫉㪊㪅㪈㩷 㫊㪿㫆㫎㩷 㫊㫀㫋㪼㫊㩷 㪽㫆㫉㩷 㫄㫆㪻㫌㫃㪸㫋㫀㫅㪾㩷 㪾㪸㫋㫀㫅㪾㩷 㪸㫅㪻㩷 ― 105 ― 昭和大学薬学雑誌 第 2 巻 第 1 号 2011 年 㫉㪼㪺㫋㫀㪽㫀㪺㪸㫋㫀㫆㫅㪅㩷 㩷 Nat. Neurosci.㩷㪏㪃㩷㪉㪎㪐㪄㪉㪏㪎㩷㩿㪉㪇㪇㪌㪀㩷 㪈㪍㪀㩷 㪢㫌㫆㪃㩷 㪘㪅㪃㩷 㪞㫌㫃㪹㫀㫊㪃㩷 㪡㪅㪤㪅㪃㩷 㪘㫅㫋㪺㫃㫀㪽㪽㪃㩷 㪡㪅㪝㪅㪃㩷 㩷 et al.㪑㩷 㪐㧕㩷 㪞㫌㫆㪃㩷 㪛㪅㪃㩷 㪣㫌㪃㩷 㪱㪅㪑㩷 㪠㫅㫋㪼㫉㪸㪺㫋㫀㫆㫅㩷 㫄㪼㪺㪿㪸㫅㫀㫊㫄㫊㩷 㪚㫉㫐㫊㫋㪸㫃㩷 㫊㫋㫉㫌㪺㫋㫌㫉㪼㩷 㫆㪽㩷 㫋㪿㪼㩷 㫇㫆㫋㪸㫊㫊㫀㫌㫄㩷 㪺㪿㪸㫅㫅㪼㫃㩷 㪂 㪹㪼㫋㫎㪼㪼㫅㩷㫇㫆㫃㫐㪸㫄㫀㫅㪼㫊㩷㪸㫅㪻㩷㪠㪩㪢㪈㩷㫀㫅㫎㪸㫉㪻㩷㫉㪼㪺㫋㫀㪽㫀㪼㫉㩷㪢 㩷 㪢㫀㫉㪙㪸㪺㪈㪅㪈㩷 㫀㫅㩷 㫋㪿㪼㩷 㪺㫃㫆㫊㪼㪻㩷 㫊㫋㪸㫋㪼㪅㩷 Science㩷 㪊㪇㪇㪃㩷 㪺㪿㪸㫅㫅㪼㫃㫊㪅㩷J. Gen. Physiol.㩷㪈㪉㪉㪃㩷㪋㪏㪌㪄㪌㪇㪇㩷㩿㪉㪇㪇㪊㪀㩷 㪈㪐㪉㪉㵨㪈㪐㪉㪍㩷㩿㪉㪇㪇㪊㪀㩷 㪈㪇㪀㩷 㪮㫀㪹㫃㪼㪃㩷㪙㪅㩷㪘㪅㪃㩷㪫㪸㪾㫃㫀㪸㫃㪸㫋㪼㫃㪸㪃㩷㪤㪅㪃㩷㪝㫀㪺㫂㪼㫉㪃㩷㪜㪅㪃㩷et al.:㩷 㪈㪎㪀㩷 㪚㪸㫆㪃㩷 㪰㪅㪃㩷 㪡㫀㫅㪃㩷 㪯㪅㪃㩷 㪟㫌㪸㫅㪾㪃㩷 㪟㪅㪃㩷 et al㪅㪑㩷 㪚㫉㫐㫊㫋㪸㫃㩷 㪂 㪞㪸㫋㫀㫅㪾㩷 㫆㪽㩷 㫀㫅㫎㪸㫉㪻㫃㫐㩷 㫉㪼㪺㫋㫀㪽㫐㫀㫅㪾㩷 㪢 㩷 㪺㪿㪸㫅㫅㪼㫃㫊㩷 㫊㫋㫉㫌㪺㫋㫌㫉㪼㩷㫆㪽㩷㪸㩷㫇㫆㫋㪸㫊㫊㫀㫌㫄㩷㫀㫆㫅㩷㫋㫉㪸㫅㫊㫇㫆㫉㫋㪼㫉㪃㩷㪫㫉㫂㪟㪅㩷 㫃㫆㪺㪸㫃㫀㫑㪼㪻㩷㫋㫆㩷㪸㩷㫊㫀㫅㪾㫃㪼㩷㫅㪼㪾㪸㫋㫀㫍㪼㫃㫐㩷㪺㪿㪸㫉㪾㪼㪻㩷㫉㪼㫊㫀㪻㫌㪼㪅㩷 Nature㩷㪋㪎㪈㪃㩷㪊㪊㪍㪄㪊㪋㪇㩷㩿㪉㪇㪈㪈㪀㩷 㪈㪏㪀㩷 㪚㫃㪸㫉㫂㪼㪃㩷 㪦㪅㪙㪅㪃㩷 㪚㪸㫇㫌㫋㫆㪃㩷 㪘㪅㪫㪅㪃㩷 㪟㫀㫃㫃㪃㩷 㪘㪅㪧㪅㪃㩷 et al.:㩷 Nature 㪊㪎㪈㪃㩷㪉㪋㪍㪄㪉㪋㪐㩷㩿㪈㪐㪐㪋㪀㩷 㪛㫆㫄㪸㫀㫅㩷 㫉㪼㫆㫉㫀㪼㫅㫋㪸㫋㫀㫆㫅㩷 㪸㫅㪻㩷 㫉㫆㫋㪸㫋㫀㫆㫅㩷 㫆㪽㩷 㪸㫅㩷 㪈㪈㪀㩷 㪣㫌㪃㩷 㪱㪅㪃㩷 㪤㪸㪺㪢㫀㫅㫅㫆㫅㪃㩷 㪩㪅㪑㩷 㪜㫃㪼㪺㫋㫉㫆㫊㫋㪸㫋㫀㪺㩷 㫋㫌㫅㫀㫅㪾㩷 㫆㪽㩷 㪉㪂 㪂 㪤㪾 㩷 㪸㪽㪽㫀㫅㫀㫋㫐㩷 㫀㫅㩷 㪸㫅㩷 㫀㫅㫎㪸㫉㪻㪄㫉㪼㪺㫋㫀㪽㫀㪼㫉㩷 㪢 㩷 㪺㪿㪸㫅㫅㪼㫃㪅㩷 㫀㫅㫋㫉㪸㪺㪼㫃㫃㫌㫃㪸㫉㩷㪸㫊㫊㪼㫄㪹㫃㫐㩷㫉㪼㪾㫌㫃㪸㫋㪼㩷㪺㫆㫅㪻㫌㪺㫋㫀㫆㫅㩷㫀㫅㩷㪢㫀㫉㩷 Nature㩷㪊㪎㪈㪃㩷㪉㪋㪊㪄㪉㪋㪍㩷㩿㪈㪐㪐㪋㪀㩷 㫇㫆㫋㪸㫊㫊㫀㫌㫄㩷㪺㪿㪸㫅㫅㪼㫃㫊㪅㩷Cell 㪈㪋㪈㪃㩷㪈㪇㪈㪏㪄㪈㪇㪉㪐㩷㩿㪉㪇㪈㪇㪀㩷 㩷 㪈㪉㪀㩷 㪱㪿㫆㫌㪃㩷㪰㪅㪃㩷㪤㫆㫉㪸㫀㫊㪄㪚㪸㪹㫉㪸㫃㪃㩷㪡㪅㪟㪅㪃㩷㪢㪸㫌㪽㫄㪸㫅㪃㩷㪘㪅㪃㩷㪼㫋㩷 㪈㪐㪀㩷 㪡㫀㪸㫅㪾㪃㩷 㪰㪅㪃㩷 㪣㪼㪼㪃㩷 㪘㪅㪃㩷 㪚㪿㪼㫅㪃㩷 㪡㪅㪃㩷 㪼㫋㩷 㪸㫃㪅㪑㩷 㪚㫉㫐㫊㫋㪸㫃㩷 㪸㫃㪅㪑㩷㪚㪿㪼㫄㫀㫊㫋㫉㫐㩷㫆㪽㩷㫀㫆㫅㩷㪺㫆㫆㫉㪻㫀㫅㪸㫋㫀㫆㫅㩷㪸㫅㪻㩷㪿㫐㪻㫉㪸㫋㫀㫆㫅㩷 㫊㫋㫉㫌㪺㫋㫌㫉㪼㩷 㪸㫅㪻㩷 㫄㪼㪺㪿㪸㫅㫀㫊㫄㩷 㫆㪽㩷 㪸㩷 㪺㪸㫃㪺㫀㫌㫄㪄㪾㪸㫋㪼㪻㩷 㪂 㫇㫆㫋㪸㫊㫊㫀㫌㫄㩷㪺㪿㪸㫅㫅㪼㫃㪅㩷Nature,㩷㪋㪈㪎㪃㩷㪌㪈㪌㪄㪉㪉㩷㩿㪉㪇㪇㪉㪀㪅㩷 㫉㪼㫍㪼㪸㫃㪼㪻㩷㪹㫐㩷㪸㩷㪢 㩷㪺㪿㪸㫅㫅㪼㫃㪄㪝㪸㪹㩷㪺㫆㫄㫇㫃㪼㫏㩷㪸㫋㩷㪉㪅㪇㩷㪘㩷 㪉㪇㪀㩷 㪠㫅㪸㫅㫆㪹㪼㪃㩷㪘㪅㪃㩷㪤㪸㫋㫊㫌㫌㫉㪸㪃㩷㪫㪅㪃㩷㪥㪸㫂㪸㪾㪸㫎㪸㪃㩷㪘㪅㪃㩷et al.㪑㩷 㫉㪼㫊㫆㫃㫌㫋㫀㫆㫅㪅㩷Nature 㪋㪈㪋㪃㩷㪋㪊㪄㪋㪏㩿㪉㪇㪇㪈㪀㩷 㪈㪊㪀㩷 㪡㫀㪸㫅㪾㪃㩷 㪰㪅㪃㩷 㪣㪼㪼㪃㩷 㪘㪅㪃㩷 㪚㪿㪼㫅㪃㩷 㪡㪅㪑㩷 㪫㪿㪼㩷 㫆㫇㪼㫅㩷 㫇㫆㫉㪼㩷 㪪㫋㫉㫌㪺㫋㫌㫉㪸㫃㩷㪻㫀㫍㪼㫉㫊㫀㫋㫐㩷㫀㫅㩷㫋㪿㪼㩷㪺㫐㫋㫆㫇㫃㪸㫊㫄㫀㪺㩷㫉㪼㪾㫀㫆㫅㩷㫆㪽㩷 㪺㫆㫅㪽㫆㫉㫄㪸㫋㫀㫆㫅㩷㫆㪽㩷㫇㫆㫋㪸㫊㫊㫀㫌㫄㩷㪺㪿㪸㫅㫅㪼㫃㫊㪅㩷Nature㩷㪋㪈㪎㪃㩷 㪞㩷 㫇㫉㫆㫋㪼㫀㫅㪄㪾㪸㫋㪼㪻㩷 㫀㫅㫎㪸㫉㪻㩷 㫉㪼㪺㫋㫀㪽㫀㪼㫉㩷 㪢㪂㩷 㪺㪿㪸㫅㫅㪼㫃㫊㪅㩷 㪌㪉㪊㪄㪌㪉㪍㩷㩿㪉㪇㪇㪉㪀㩷 Channels 㪈㪃㩷㪊㪐㪄㪋㪌㩷㩿㪉㪇㪇㪎㪀㩷 㪈㪋㪀㩷 㪫㪸㫆㪃㩷㪯㪅㪃㩷㪘㫍㪸㫃㫆㫊㪃㩷㪡㪅㩷㪣㪅㪃㩷㪚㪿㪼㫅㪃㩷㪡㪅㪃㩷et al.㪑㩷㪚㫉㫐㫊㫋㪸㫃㩷 㫊㫋㫉㫌㪺㫋㫌㫉㪼㩷 㫆㪽㩷 㫋㪿㪼㩷 㪼㫌㫂㪸㫉㫐㫆㫋㫀㪺㩷 㪉㪈㪀㩷 㪪㪿㫀㪃㩷 㪥㪅㪃㩷 㪰㪼㪃㩷 㪪㪅㪃㩷 㪘㫃㪸㫄㪃㩷 㪘㪅㪃㩷 et al.㪑㩷 㪘㫋㫆㫄㫀㪺㩷 㫊㫋㫉㫌㪺㫋㫌㫉㪼㩷㫆㪽㩷㪸㩷㪥㪸㪂㪄㩷㪸㫅㪻㩷㪢㪂㪄㪺㫆㫅㪻㫌㪺㫋㫀㫅㪾㩷㪺㪿㪸㫅㫅㪼㫃㪅㩷 㫊㫋㫉㫆㫅㪾㩷 㫀㫅㫎㪸㫉㪻㪄㫉㪼㪺㫋㫀㪽㫀㪼㫉㩷 㪢㪂㩷 㪺㪿㪸㫅㫅㪼㫃㩷 㪢㫀㫉㪉㪅㪉㩷 㪸㫋㩷 㪊㪅㪈㩷 㪘㩷 㫉㪼㫊㫆㫃㫌㫋㫀㫆㫅㪅 Science㩷㪊㪉㪍㪃㩷㪈㪍㪍㪏㪄㪎㪋㩿㪉㪇㪇㪐㪀㩷 Nature㩷㪋㪋㪇㪃㩷㪌㪎㪇㪄㪌㪎㪋㩷㩿㪉㪇㪇㪍㪀㩷 㩷 㪈㪌㪀㩷 㪥㫀㫊㪿㫀㪻㪸㪃㩷 㪤㪅㪃㩷 㪚㪸㪻㪼㫅㪼㪃㩷 㪤㪅㪃㩷 㪚㪿㪸㫀㫋㪃㩷 㪙㪅㩷 㪫㪅㪃㩷 et al.㪑㩷 㪚㫉㫐㫊㫋㪸㫃㩷 㫊㫋㫉㫌㪺㫋㫌㫉㪼㩷 㫆㪽㩷 㪸㩷 㪢㫀㫉㪊㪅㪈㪄㫇㫉㫆㫂㪸㫉㫐㫆㫋㫀㪺㩷 㪢㫀㫉㩷 㪺㪿㪸㫅㫅㪼㫃㩷㪺㪿㫀㫄㪼㫉㪸㪅㩷EMBO J㪅㩷㪉㪍㪃㩷㪋㪇㪇㪌㪄㪈㪌㩷㩿㪉㪇㪇㪎㪀㩷 ― 106 ― 昭和大学薬学雑誌 第 2 巻 第 1 号 2011 年 Structure Analysis of the novel potassium channel and a brief introduction of Oxford University Yoshio Kusakabe 㪛㪼㫇㪸㫉㫋㫄㪼㫅㫋㩷㫆㪽㩷㪧㪿㫐㫊㫀㪺㪸㫃㩷㪺㪿㪼㫄㫀㫊㫋㫉㫐㪃㩷㪪㪿㫆㫎㪸㩷㪬㫅㫀㫍㪼㫉㫊㫀㫋㫐㩷㪪㪺㪿㫆㫆㫃㩷㫆㪽㩷㪧㪿㪸㫉㫄㪸㪺㫐㩷 㩷 Abstract Potassium channels are present in nearly all cells, from bacteria to plants and animals. They participate in process ranging from cell volume regulation to the generation of electrical impulses in excitable cells.Inwardly-rectifying potassium channels are regulated by many different cellular factors such as G-proteins, PIP2, ATP and intracellular pH, and are therefore able to couple channel activity to a wide range of metabolic and physiological stimuli. Their importance is illustrated by the fact that inherited mutations in Kir channels underlie a number of diseases. All K+ channels share a conserved selectivity filter that permits K+ ion passage and excludes Na+. Potassium ions flow through the pore passively, into or out of the cell, depending on the direction of the electrochemical gradient. For most K+ channels, given equal but oppositely directed gradients, K+ ions flow with about the same kinetic efficiency in either direction. Certain K+ channels, forming a distinct subset known as inward rectifiers or IRK channels, are unique in that they conduct K+ ions more efficiently in one direction into the cell. In this study, we set out to understand the structure of a K+ channels. Why do they rectify and how might the protein control their gating? To begin to address these questions, we have tried the atomic structure of the K+ channel by X-ray crystallography. Key Words㧦University of Oxoford, structure determination, potossium channel 㪩㪼㪺㪼㫀㫍㪼㪻㩷㪋㩷㪘㫇㫉㫀㫃㩷㪉㪇㪈㪈㪒㩷㪸㪺㪺㪼㫇㫋㪼㪻㩷㪊㩷㪡㫌㫅㪼㩷㪉㪇㪈㪈㪅㩷 㩷 㩷 ― 107 ―
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